Zajc Laboratories

Organofluorine, Bioorganic, and Methodological Chemistry

INTRODUCTION

Prof. Zajc’s research is in the area of organofluorine chemistry, with the focus on development of novel regiospecific fluorination methods, and the use of fluorine as a probe in studies related to metabolism and biological activity of environmental pollutants. The importance for this area of research is exemplified in the fact that over 25% commercial pharmaceuticals
contain fluorine atom.In the area of methods development, novel fluorinated building blocks are synthesized and
their reactivities are studied. These building blocks are then used for polyfunctionalization, via
a modular synthesis approach. Specifically, we are developing a series of fluorinated Julia-
Kocienski reagents, where fluorine atom is introduced via metalation-electrophilic fluorination.
To gain a deeper understanding of the chemical methodology, reactivities of these reagents
are studied in olefination reactions, and also compared with unfluorinated analogs. The
overall goal of our work is the development of a chemical fluoroolefination toolbox for the
synthesis of diverse functionalized fluorinated alkenes. We are also involved with the
development of biologically important compounds, such as potential anti-tumor and antiviral
agents, via our fluorination chemistry approaches.This area overlaps with our interests in catalysis chemistry as well as the chemistry and biology of polycyclic aromatic hydrocarbons. Additionally, we are also developing uncatalyzed methods for nucleoside modification. In this context we have been exploring unusual reactions of peptide coupling agents for transformations that have not previously been studied. Some of the chemical developments herein contribute to the generation of new synthetic methodology as well.

In studies related to the influence of environmental pollutants on human health, we are
utilizing fluorine atom to modulate biological activity. In this area, research involves synthesis
of fluorinated analogs of environmental pollutants, their putative metabolites and DNA
conjugates, for structure activity studies. This often entails the development of stereoselective
methodologies, evaluation of chirality in products, and multistep syntheses.

Reactions we have developed towards a flexible fluoroolefination toolbox